Intrathecal Opioid Analgesia

This page is included on account of the 2019 SAQ on this topic (57% pass rate), in which a question on 'the mechanism of action of intrathecal opioids was answered poorly'.

Resources

Current approaches to acute postoperative pain management after major abdominal surgery: a narrative review and future directions (BJA, 2022)
Acute Pain Management: Scientific Evidence, 5th Edition, Section 5.7 (Australian and New Zealand College of Anaesthetists and Faculty of Pain Medicine, 2020)

Opioids administered intrathecally produce more potent and prolonged analgesic action than systemic opioids, but suffer from a number of issues

Commonly used

Morphine 75-300μg
Diamorphine 200-300μg
Fentanyl 12.5-50μg

Other opioids

Hydromorphone 5-10μg
Buprenorphine
Pethidine (meperidine)
Sufentanil
Tramadol
Pentazocine

Adjuncts

Clonidine (25-75μg) or Dexmedetomidine (5μg)

Prolong block and synergistic analgesic effect
Issues include significant hypotension, as well as bradycardia and sedation

Magnesium

Spinal cord

Primarily function by inhibiting nociceptive pathways in the spinal cord

Reducing afferent signalling

Opioid is injected intrathecally
Binds to pre-synaptic G-protein coupled (G_i) opioid receptors in laminae I and II of the dorsal horn of the spinal cord i.e. the substantia gelatinosa
Within the neuron there is:

Inhibition of adenylyl cyclase, reducing cAMP levels
Increased K⁺ channel conductance
Reduced Ca²⁺ channel conductance
An overall hyperpolarisation of the cell membrane and reduction of neuronal cell excitability

There is reduced release of neurotransmitters from afferent nociceptive neurones
Overall reduced pain signal transmission

Increasing activity at descending inhibitory pathways to the dorsal horn

Descending inhibitory pathways from the from the PAG via the nucleus raphe magnus modulate ascending (afferent) pain transmission
These pathways are themselves subject to inhibition by GABA-ergic interneurones
Opioids imapir GABA release from these interneurones
There is thus 'inhibition of the inhibitors' i.e. opioids cause activation of the inhibitory descending pathways
This further dampens ascending (afferent) nocicpetive neuronal transmission

Benefits of intrathecal opioids

Clinically significant opioid-sparing effect

Prolongs duration of spinal analgesia

Improved pain at rest at 24hrs

Improved dynamic pain at 48hrs

Overall reduced pain scores for up to 72hrs

Marginally reduced hospital length of stay

High patient satisfaction

Suitable in patients where coagulopathy precludes catheter-based techniques

Incidence of some side-effects is not different to systemic opioids

Finite duration of effect
May be less effective than epidural analgesia for some patient groups
Standard opioid-induced side-effects: nausea, vomiting, urinary retention, hypotension

Pruritus

Dose-dependent, significantly higher rates of pruritis than for systemic opioids:

30-40% for morphine overall, but 60-100% in the obstetric population
27% for IT fentanyl

Mechanisms

Stimulation of spinal and supraspinal mu-opioid receptors, including the trigeminal nucleus causing facial itch
Dose-dependent increases in plasma serotonin levels (approx. 550% following 250μg intrathecal morphine)

Management

Ondansetron 4-8mg is effective for treating established pruritus and has a preventative effect in non-obstetric populations
Naloxone or other partial opioid antagonists such as nalbuphine or pentazocine
Mirtazepine
Droperidol

Respiratory depression a.k.a opioid-induced ventilatory impairment (OIVI)

There are issues in assessing and comparing this side-effect due to:

Large sample size requirements for such an infrequent event
Inconsistent definitions, variably using respiratory rate, desaturation or need for supplemental oxygen, or need for opioid antagonists

The timing of respiratory depression with morphine is delayed, with peak effects at 4-8hrs and altered ventilatory response to CO2 up to 20hrs

In overall summary:

IT morphine is more likely to cause respiratory depression than IT fentanyl
The risk of respiratory depression with morphine will depend on definition used, opioid used, patient cohort and surgery performed but generally ranges from 1-9%
Respiratory depression is more likely at higher (>300μg) morphine doses
The rate of respiratory depression with low dose IT morphine may be (near-) equivalent to that of systemic opioids
The lowest effective dose of IT morphine should be used in order to reduce the risk of delayed respiratory depression
Patients who've received IT opioids should have monitoring for OIVI for 18-24hrs post-operatively